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Vaping-induced lung injury: a 21st century health crisis

Presenter: Jack Chang, PharmDInfectious Diseases Pharmacotherapy FellowMidwestern University Chicago College of Pharmacy

Project mentor:

Chris Leong, PharmD, BCCCPCritical Care Team Leader, Clinical PharmacistNorthwestern Memorial Hospital

Conflict of interest declaration

Neither the presenter (Jack Chang, PharmD) nor project mentor (Chris Leong, PharmD, BCCCP)

have any conflicts of interest to declare.

Objectives:

1. Review the history, epidemiology, and pathophysiology of electronic-cigarette or vaping product use-associated lung injury (EVALI).

2. Identify known causes of EVALI

3. Describe the typical presentation of a patient with EVALI

4. Review and discuss case reports relating to EVALI

5. Discuss current treatment strategies for EVALI

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Overview of electronic-cigarette or vaping product use-associated lung

injury (EVALI)

Background:What is EVALI?

• Electronic cigarette (e-cigarette), or vaping, product-use associated lung injury was first reported to the Centers for Disease Control and Prevention (CDC) on August 1, 2019.1

• EVALI describes a spectrum of lung dysfunction that is associated with vaporization of nicotine, cannabinoid products, and other chemicals.2

• Outbreak of this disease is particularly concerning since severe, sometimes fatal symptoms can occur rapidly in otherwise healthy, young individuals.

1. Hartnett KP, Kite-Powell A, Patel MT, et al. Syndromic surveillance of e-cigarette, or vaping, product-use associated lung injury. N Engl J Med. 2019. 2. U.S. Food & Drug Administration (2019). Lung illness associated with use of vaping products. Retrieved from https://www.fda.gov/news-events/public-health-focus/lung-illnesses-associated-use-vaping-products

State and Federal warnings related to EVALI 3,4

63. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.4. Centers for Disease Control and Prevention (2019). Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. Retrieved from https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#latest-outbreak-information.

July 25, 2019

• WiscosinDepartment of Public Health Services issues health advisory

August 2, 2019

• Illinois Department of Public Health issues health advisory

August 30, 2019

• CDC issues national health advisory

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History: Timeline of EVALI cases

Image courtesy of New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMsr1915313. Accessed January 4, 2020.

Epidemiology:Distribution of EVALI cases

Image courtesy of Centers for Disease Control and Prevention. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#latest-outbreak-information. Accessed January 4, 2020.

Epidemiology:Distribution of EVALI cases

Image courtesy of Illinois Department of Public Health. http://www.dph.illinois.gov/topics-services/prevention-wellness/tobacco/e-cigarettes-and-vapes. Accessed January 4, 2020.5. Illinois Department of Public Health (2019). E-cigarettes and vapes. Retrieved from http://www.dph.illinois.gov/topics-services/prevention-wellness/tobacco/e-cigarettes-and-vapes.

- Illinois had 206 reported EVALI cases in 2019, with 5 associated fatalities.5

- Median age of affected patients was 22 yrs(range 13-85 years old).

- 2017 data for U.S. and Illinois high school students:

- 42% reported having ever used an electronic vapor product

- 13% were current users

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Assessment question:

Which age group showed the greatest increase in recent EVALI cases?

A. 10-19 years old

B. 20-29 years old

C. 30-39 years old

D. >65 years old

Current known causes of EVALI

Causes of EVALI:Devices

Image courtesy of Centers for Disease Control and Prevention. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/about-e-cigarettes.html. Accessed January 4, 2020.

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Causes of EVALI:Devices

Image courtesy of Union for International Cancer Control. https://www.fda.gov/tobacco-products/products-ingredients-components/vaporizers-e-cigarettes-and-other-electronic-nicotine-delivery-systems-ends. Accessed January 4, 2020.

Image courtesy of King County Health Department. https://www.kingcounty.gov/depts/health/tobacco/data/e-cigarettes.aspx. Accessed January 4, 2020

Causes of EVALI:Devices

Battery Heating element Vaporized liquid(‘E-juice’)

Causes of EVALI:What is in e-cigarettes?

Image courtesy of Centers for Disease Control and Prevention. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/about-e-cigarettes.html. Accessed January 4, 2020.

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Causes of EVALI:What is in e-cigarettes?

16

6. U.S. Food and Drug Administration (2019). Lung illness associated with use of vaping products: information for the public, FDA actions, and recommendations. Retrieved from https://www.fda.gov/news-events/public-health-focus/lung-illnesses-associated-use-vaping-products.

7. Public Health Consequences of E-Cigarettes. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems; Eaton DL, Kwan LY, Stratton K, editors.

Washington (DC): National Academies Press (US); 2018 Jan 23.

- Recent testing by the U.S. Food and Drug Administration and other laboratories has found a number of chemicals in e-cigarettes 6,7

- Nicotine

- Tetrahydrocannabinol (THC)

- Vitamin E acetate

- Aldehydes (flavoring)

- Acetals (flavoring)

- Metals

- Carbonyl compounds (carcinogens)

- Polyethylene glycol (solvent)

- Glycerol (solvent)

- Tobacco-specific nitrosamines- Free radicals and reactive oxygen

species- Furans- Phthalates- Microorganisms- Pharmaceutical drugs- And others…

Causes of EVALI:Link between vitamin E acetate and lipoid pneumonia• Although many potential causes of EVALI have been identified, the causative agents

have not been established.

• One recent study examined bronchoalveolar lavage (BAL) samples from EVALI patients.8

8. Blount BC, Karwowski MP, Shields PG, et al. Vitamin e acetate in bronchoalveolar-lavage fluid associated with EVALI. N Engl J Med. 2019. doi: 10.1056/NEJMoa1916433

Methods: - 51 BAL samples were collected from patients with EVALI in 16 states- Measured levels of: vitamin E acetate, plant oils, medium-chain triglyceride oil,

petroleum distillates, and diluent terpenes

Results: - Vitamin E acetate was identified in 94% of EVALI patient BAL samples (not identified in healthy controls)

- 94% of samples had detectable THC or metabolites- 64% of samples had detectable nicotine or metabolites

Conclusion: - Vitamin E acetate was associated with EVALI in this convenience sample.

Health effects of using e-cigarettes:

Nicotine and THC:

- Both are highly addictive drugs- Associated with harm to adolescent brain development- Health danger to pregnant women and developing babies

Aerosol: - E-cigarette aerosols can contain cancer causing chemicals- Generally contain fewer harmful chemicals than smoke

from combusted tobacco products

Device: - Defective e-cigarette batteries have been reported to cause fires and explosions, sometimes resulting in serious injuries.9

9. US Department of Health and Human Services. E-cigarette use among youth and young adults: a report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, CDC; 2016.

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Assessment question:

Which of the following chemicals has been found to be associated with development of EVALI?

A. Polyethylene glycol

B. Vitamin E acetate

C. THC

Pathophysiology and presentation of patients with EVALI

Pathophysiology:• Despite increasing case reports and evidence for EVALI, the pathology is still poorly understood.

• Histopathological findings generally show acute lung injury patterns.10,11

10. Butt YM, Smith ML, Tazelaar HD, et al. Pathology of vaping-associated lung injury. N Engl J Med. 2019;381(18):1780-1781.11. Arter ZL, Wiggins A, Hudspath C, et al. Acute eosinophilic pneumonia following electronic cigarette use. Respir Med Case Rep. 2019 Mar 18;27:100825

Presentation Radiologic findings BAL findings

Acute eosinophilic pneumonia

- Acute onset, severe symptoms - Septal thickening- Pleural effusion

- Eosinophilia

Organizing pneumonia

- Subacute onset, variable severity

- Nodular ground glass opacities

- Nonspecific

Lipoid pneumonia - Subacute onset, chronic fevers, weight loss

- ‘Crazy paving’ - Lipid-laden macrophages

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PathophysiologyRadiologic findings• Can present with a variety of imaging patterns but majority

of cases have septal thickening, basilar-predominant opacities, and ground-glass opacities.

• Some overlapping imaging findings with other acute inhalation injuries:

- Ex. Acute eosinophilic pneumonia and diffuse alveolar damage

21. Henry TS, Kanne JP, Kligerman SJ. Imaging of vaping-associated lung disease. N Engl J Med. 2019. doi: 10.1056/NEJMc1911995.

Risk factors for EVALI

- Pre-existing lung disease12

- COPD, asthma, concurrent bacterial or viral pneumonia

- Increased incidence with younger age (18-24 years old)12,13

- Increased mortality with older age (>50 years old)14

- Recent or continued use of electronic vaping products

- Use of black market or illegal nicotine and THC products.12

12. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.13. Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med 2019;381:1488–914. Mikosz CA, Danielson M, Anderson KN, et al. Characteristics of Patients Experiencing Rehospitalization or Death After Hospital Discharge in a Nationwide Outbreak of E-cigarette, or Vaping, Product Use–Associated Lung Injury — United States, 2019. MMWR Morb Mortal Wkly Rep 2020;68:1183-1188.

Signs and symptoms of EVALI

Respiratory

(98% incidence)

• Dyspnea

• Hypoxia

• Chest pain

• Cough

• Hemoptysis

Gastrointestinal

(81% incidence)

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

Constitutional

(100% incidence)

• Fever

• Chills

• Headache

• Weight loss

• Fatigue/ malaise

12. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.

*Upper respiratory symptoms do not appear to be a typical component of EVALI.12

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Signs and symptoms of EVALILaboratory findings 12,13

12. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.

13. Maddock SD et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019;381:1488-1489.

CBC

• WBC elevation

• Neutrophilia (>80% neutrophils)

Acute phase reactants

• ESR elevation

• CRP elevation

• Procalcitoninelevation

BAL findings

• Neutrophils

• Lipid-laden macrophages (seen on Oil Red-O stain)

CBC: complete blood countWBC: white blood cellsESR: erythrocyte sedimentation rateCRP: C-reactive protein

Importance of vaping history- Almost all cases of EVALI involve both frequent use (≥ 5 times per day)

and recent or current use of vaping products.

- Assessment of e-cigarette or vaping product use is important for patients who present with respiratory, gastrointestinal, or constitutional symptoms.15

- Approach patient interviews with an empathetic and non-judgementalmanner.

- Adolescents and young adults are more likely to share sensitive information when parents/ guardians step outside the exam room.

15. Centers for Disease Control and Prevention (2019). Assessing the risk of lung injury in patients using e-cigarette, or vaping, products. Retrieved from https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease/healthcare-providers/pdfs/dont-forget-to-ask-assessing-the-risk-of-lung-injury-508.pdf.

Assessment of vaping history

15. Centers for Disease Control and Prevention (2019). Assessing the risk of lung injury in patients using e-cigarette, or vaping, products. Retrieved from https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease/healthcare-providers/pdfs/dont-forget-to-ask-assessing-the-risk-of-lung-injury-508.pdf.

What

• Ask patients if they have used or tried e-cigarettes or vaping products.

• Most EVALI cases involved use of THC-containing products.

How

• Ask how often and when patients last used vaping products.

• Many EVALI patients report frequent usage (≥5 times per day).

Where

• Ask where the e-cigarette or vaping products were obtained.

• Most EVALI cases involve illegal or non-commercial sources.

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Clinical evaluation of suspected EVALI

1. History

2. Physical exam

3. Lab testing:- Infectious diseases evaluation: respiratory viral panel, COVID-19 PCR

- Laboratory evaluation: CBC with differential, LFTs, ESR, CRP

4. Imaging:- Chest radiograph with consideration for CT scan for more severe presentation.

Presentation or Section Title

Assessment question

Which of the following is not a common symptom of EVALI?

A. Respiratory distress

B. Nausea and vomiting

C. Renal failure

D. Fever

Course and Diagnosis of EVALI

Initial respiratory symptoms

Development of respiratory

failure

Hospitalization and possible

ICU care

- EVALI remains a diagnosis of exclusion.1

- Many patients receive antibiotics initially and experience symptom progression.

- Patients with pre-existing lung disease (asthma, COPD, sleep apnea) may be more prone to hospitalization, rehospitalization, and death due to EVALI.2

12. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.14. Mikosz CA, Danielson M, Anderson KN, et al. Characteristics of Patients Experiencing Rehospitalization or Death After Hospital Discharge in a Nationwide Outbreak of E-cigarette, or Vaping, Product Use–Associated Lung Injury — United States, 2019. MMWR Morb Mortal Wkly Rep 2020;68:1183-1188.

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Case series on EVALI

Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019;381:1488–9.16

PMH: 25 yo female with Hashimoto’s thyroiditis presented to an OSH with one week history of cough, dyspnea, fevers, chills, and myalgias. Similar episode 2 months ago that spontaneously resolved. - Endorsed daily vaping of THC-containing products

Labs:- ESR and CRP elevated- BAL ~50% lipid laden macrophages (LLM)Imaging:- CT chest showed patchy bilateral basilar opacities with interstitial prominence

Treatment:- Ceftriaxone/ azithromycin- Prednisone 60mg daily- Supplemental oxygen via nasal canula

Disease course and outcome:- Required transfer for worsening respiratory failure requiring supplemental oxygen via high-flow nasal cannula.- Completed ceftriaxone/ azithromycin course and was discharged on prednisone taper.

PMH: 29 yo male with no prior medical history presented to an OSH with two weeks of fever, sweats, weakness, myalgias, and weight loss. - Endorsed daily vaping

Labs:- Elevated ESR, CRO, and antinuclear antibody titer- BAL with ~30% LLMsImaging:- Chest imaging with multifocal opacities

Inpatient treatment:- Ceftriaxone and azithromycin- Supplemental oxygen via nasal canula

Disease course and outcome:- Transferred after initial treatment for CAP with ceftriaxone, azithromycin, and glucocorticoids was unsuccessful.- Completed a subsequent course of ceftriaxone and azithromycin and was discharged home without supplemental oxygen.

Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019;381:1488–9.16

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PMH: 23 yo male with history of polysubstance abuse (alcohol, cocaine, and marijuana) presented with wheezing, chest congestion, cough, fevers, weakness, and myalgias for two months. - Symptoms reportedly improved with outpatient antibiotics (azithromycin, doxycycline)- Endorsed daily vaping of nicotine and THC products for >3 years

Labs:- Elevated ESR, CRP, and immoglobulin E- BAL showed ~25% LLMsImaging:- Chest imaging showed diffuse ground glass opacities

Treatment:- Ceftriaxone and azithromycin- Supplemental oxygen via nasal canula

Disease course and outcome:- Transferred after he presented to an OSH with hypoxemia requiring supplemental oxygen- Completed course of ceftriaxone and azithromycin and was discharged home without supplemental oxygen.

Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019;381:1488–9.16

PMH: 23 yo male with no prior medical history who presented with a five-day history of fever, nausea, vomiting, abdominal pain, and fatigue. - Treated as an outpatient with ciprofloxacin for presumed GI infection, with no relief.- Endorsed daily vaping of THC products for the past 6 months

Labs:- Elevated ESR, CRP, and leukocytosis- BAL showed >75% LLMsImaging:- Chest imaging showed diffuse ground glass opacities

Treatment:- Supportive care- Supplemental oxygen via nasal canula

Disease course and outcome:- Presented with hypoxemia requiring supplemental oxygen.- Symptoms improved with supportive care and patient was discharged home without supplemental oxygen.

Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019;381:1488–9.16

PMH: 21 yo male with no prior medical history presented with dyspnea, cough, nausea, vomiting and abdominal pain for 1 week.- Endorsed daily vaping of nicotine and THC products

Labs:- Elevated CRP- BAL showed >50% LLMsImaging:- Chest imaging showed bilateral interstitial opacities

Treatment:- Ceftriaxone and azithromycin- Methylprednisolone 1mg/kg body weight- Mechanical ventilation and ECMO

Disease course and outcome:- Empirically treated for bacterial pneumonia but subsequently deteriorated and required intubation for acute respiratory distress syndrome. Then required ECMO for 7 days for refractory hypoxemia. - Discharged home 2 weeks after initial presentation without supplemental oxygen.

Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019;381:1488–9.16

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Reflect and review(take 1 minute to think about the following)

1. What are common presenting characteristics patients with EVALI?

2. What are some of the medications that were used to treat EVALI in the cases discussed?

Treatment strategies and prevention of EVALI

Treatment of EVALI

• Suggested empiric therapy for EVALI is similar to empiric pneumonia therapy since initial symptoms are similar:•Antibiotics (e.g. ceftriaxone and azithromycin)• Corticosteroids•Antiviral therapy•Oxygen support as necessary• Supportive care (e.g. intubation, ECMO)

17. Siegel DA, Jatlaoui TC, Koumans EH, et al. Update: Interim Guidance for Health Care Providers Evaluating and Caring for Patients with Suspected E-cigarette, or Vaping, Product Use Associated Lung Injury — United States, October 2019. MMWR Morb Mortal Wkly Rep 2019;68:919–927.18. Davidson K, Brancato A, Heetderks P, et al. Outbreak of electronic-cigarette–associated acute lipoid pneumonia—North Carolina, July–August 2019. MMWR Morb Mortal Wkly Rep 2019;68:784–6.

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Corticosteroids in EVALI• Corticosteroids may be helpful in treating EVALI.12,17

• Mechanism is likely related to blunting of inflammatory response.

• Dosing in case reports:• Most documented cases used IV methylprednisolone or oral

prednisone• Doses ranged widely:

• IV Methylprednisolone 120mg to 500mg daily18

• IV Methylprednisolone 1mg/kg/day16

• Oral Prednisone 60mg daily16

12. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin—preliminary report. N Engl J Med. 2019.16. Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med 2019;381:1488–917. Siegel DA, Jatlaoui TC, Koumans EH, et al. Update: Interim Guidance for Health Care Providers Evaluating and Caring for Patients with Suspected E-cigarette, or Vaping, Product Use Associated Lung Injury — United States, October 2019. MMWR Morb Mortal Wkly Rep 2019;68:919–927.18. Davidson K, Brancato A, Heetderks P, et al. Outbreak of electronic-cigarette–associated acute lipoid pneumonia—North Carolina, July–August 2019. MMWR Morb Mortal Wkly Rep 2019;68:784–6.

Corticosteroid dosing in EVALIStudy Steroid dosing Outcome

5 patients in two North Carolina hospitals18

Methylprednisolone 125-500mg daily

All 5 patients survived- 3 required ICU care- 1 required mechanical ventilation

Case series of 53 patients in Illinois and Wisconsin12

46/53 (92%) of patients received systemic glucocorticoids- Dosing not provided

- Median duration of therapy was ≥ 7 days- Analysis of 5 cases showed that extubation occurred 5-10 days after initiating steroids.

12. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.18. Davidson K, Brancato A, Heetderks P, et al. Outbreak of Electronic-Cigarette-Associated Acute Lipoid Pneumonia - North Carolina, July-August 2019. MMWR Morb Mortal Wkly Rep. 2019;68(36):784.

Corticosteroid dosing in EVALIStudy Care status Steroid dosing Outcome

Case series of 60 patients in Utah 19

ICU (33/60) Methylprednisolone (32/60)- Median initial dose: 125 mg/day(IQR: 100-240 mg)- Median duration: 15 days (IQR: 10-34 days)

5 readmitted to hospital or ICU

Inpatient (21/60)

Methylprednisolone (10/21)- Median initial dose: 125 mg/day(IQR: 125-240 mg)- Median duration: 10 days (IQR: 8-13 days)Prednisone (10/21)- Median initial dose: 50 mg/day(IQR: 40-60 mg)- Median duration: 7 days (IQR: 5-11 days)

1 readmitted to hospital or ICU

19. Blagev DP, Harris D, Dunn AC, et al. Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study. Lancet. 2019;394:2077-2083.

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Corticosteroid dosing in EVALI• No current guidelines exist on management of EVALI and corticosteroid dosing.• Available body of case reports utilize IV methylprednisolone or oral prednisone

and have reported recovery in the majority of patients receiving.

• Recommendations based on case reports:1,2

• ICU patients: Methylprednisolone 125-500 mg/day• Inpatients: Prednisone 40-60 mg/day

• Duration:3

• Most patients received steroids for 1-2 weeks, with taper over 5-10 days

12. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.18. Davidson K, Brancato A, Heetderks P, et al. Outbreak of Electronic-Cigarette-Associated Acute Lipoid Pneumonia - North Carolina, July-August 2019. MMWR Morb Mortal Wkly Rep. 2019;68(36):784.19. Blagev DP, Harris D, Dunn AC, et al. Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study. Lancet. 2019;394:2077-2083.

Prevention

• Include screening questions regarding e-cigarette or vaping use for all patients ≥10 years old.

•Educate youth and parents regarding the dangers of vaping.

•Encourage patients who vaporize nicotine to use FDA-approved methods of nicotine replacement instead.20

20. U.S. Food and Drug Administration (2019). How to quit. Retrieved from https://smokefree.gov/tools-tips/how-to-quit.

Recap

• Electronic-cigarette or vaping product use-associated lung injury (EVALI) is a respiratory disease with increasing incidence.

•Most cases are seen among young adults (12-28 years old)

• Vitamin E acetate is the only chemical that has been directly linked to EVALI so far.

• Corticosteroids appear to be helpful in treating EVALI, based on recent case reports.

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References1. Hartnett KP, Kite-Powell A, Patel MT, et al. Syndromic surveillance of e-cigarette, or vaping, product-use associated lung injury. N Engl J Med. 2019.

2. U.S. Food & Drug Administration (2019). Lung illness associated with use of vaping products. Retrieved from https://www.fda.gov/news-events/public-health-focus/lung-

illnesses-associated-use-vaping-products.

3. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.

4. Centers for Disease Control and Prevention (2019). Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. Retrieved from

https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#latest-outbreak-information.

5. Illinois Department of Public Health (2019). E-cigarettes and vapes. Retrieved from http://www.dph.illinois.gov/topics-services/prevention-wellness/tobacco/e-cigarettes-and-

vapes.

6. U.S. Food and Drug Administration (2019). Lung illness associated with use of vaping products: information for the public, FDA actions, and recommendations. Retrieved from

https://www.fda.gov/news-events/public-health-focus/lung-illnesses-associated-use-vaping-products.

7. Public Health Consequences of E-Cigarettes. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public

Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems; Eaton DL, Kwan LY, Stratton K, editors. Washington (DC): National

Academies Press (US); 2018 Jan 23.

8. Blount BC, Karwowski MP, Shields PG, et al. Vitamin e acetate in bronchoalveolar-lavage fluid associated with EVALI. N Engl J Med. 2019. doi: 10.1056/NEJMoa1916433.

9. US Department of Health and Human Services. E-cigarette use among youth and young adults: a report of the Surgeon General. Atlanta, GA: US Department of Health and

Human Services, CDC; 2016.

10. Butt YM, Smith ML, Tazelaar HD, et al. Pathology of vaping-associated lung injury. N Engl J Med. 2019;381(18):1780-1781.

11. Arter ZL, Wiggins A, Hudspath C, et al. Acute eosinophilic pneumonia following electronic cigarette use. Respir Med Case Rep. 2019 Mar 18;27:100825

12. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin — preliminary report. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911614.

13. Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med 2019;381:1488–9

14. Mikosz CA, Danielson M, Anderson KN, et al. Characteristics of Patients Experiencing Rehospitalization or Death After Hospital Discharge in a Nationwide Outbreak of E-

cigarette, or Vaping, Product Use–Associated Lung Injury — United States, 2019. MMWR Morb Mortal Wkly Rep 2020;68:1183-1188.

15. Centers for Disease Control and Prevention (2019). Assessing the risk of lung injury in patients using e-cigarette, or vaping, products. Retrieved from

https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease/healthcare-providers/pdfs/dont-forget-to-ask-assessing-the-risk-of-lung-injury-508.pdf.

Presentation or Section Title 46

References16. Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med 2019;381:1488–9.

17. Siegel DA, Jatlaoui TC, Koumans EH, et al. Update: Interim Guidance for Health Care Providers Evaluating and Caring for Patients with Suspected E-cigarette, or Vaping, Product

Use Associated Lung Injury — United States, October 2019. MMWR Morb Mortal Wkly Rep 2019;68:919–927.

18. Davidson K, Brancato A, Heetderks P, et al. Outbreak of electronic-cigarette–associated acute lipoid pneumonia—North Carolina, July–August 2019. MMWR Morb Mortal Wkly

Rep 2019;68:784–6.

19. Blagev DP, Harris D, Dunn AC, et al. Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational

cohort study. Lancet. 2019;394:2077-2083.

20. U.S. Food and Drug Administration (2019). How to quit. Retrieved from https://smokefree.gov/tools-tips/how-to-quit.

21. Henry TS, Kanne JP, Kligerman SJ. Imaging of vaping-associated lung disease. N Engl J Med. 2019. doi: 10.1056/NEJMc1911995.

Presentation or Section Title 47